What is the recommended Paxlovid (nirmatrelvir/ritonavir) dosing regimen for mild‑to‑moderate COVID‑19, including dose adjustments for impaired renal function (eGFR) and hepatic impairment, and considerations for pregnancy?

Paxlovid Dosing Regimen

The standard dose of Paxlovid is nirmatrelvir 300 mg (two 150 mg tablets) with ritonavir 100 mg (one 100 mg tablet) taken together twice daily for 5 days, initiated within 5 days of symptom onset. 1, 2

Standard Dosing Protocol

• Administer nirmatrelvir 300 mg with ritonavir 100 mg orally every 12 hours for 5 days 1, 2
• Treatment must begin as early as possible after COVID-19 diagnosis and within 5 days of symptom onset 1, 2
• Take with or without food at approximately the same time each day 2
• Nirmatrelvir must always be co-administered with ritonavir—never give nirmatrelvir alone 2

Renal Impairment Dose Adjustments

Mild Renal Impairment (eGFR ≥60 to <90 mL/min)

• No dose adjustment required—use standard 300 mg/100 mg twice daily for 5 days 2

Moderate Renal Impairment (eGFR ≥30 to <60 mL/min)

• Reduce to nirmatrelvir 150 mg (one 150 mg tablet) with ritonavir 100 mg (one 100 mg tablet) twice daily for 5 days 1, 2, 3
• This dose reduction is based on pharmacokinetic data showing 187% increased nirmatrelvir exposure in moderate renal impairment 3

Severe Renal Impairment (eGFR <30 mL/min)

• Day 1: nirmatrelvir 300 mg (two 150 mg tablets) with ritonavir 100 mg (one 100 mg tablet) once 2
• Days 2-5: nirmatrelvir 150 mg (one 150 mg tablet) with ritonavir 100 mg (one 100 mg tablet) once daily 2
• This reduced frequency accounts for 304% increased nirmatrelvir exposure in severe renal impairment 3

Hemodialysis Patients

• Follow the severe renal impairment dosing schedule above 2
• On hemodialysis days, administer Paxlovid after hemodialysis is completed 2
• Monitor for signs of drug accumulation including dysgeusia and diarrhea, which may be more pronounced with higher drug levels 4
• Reassess renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury 4

Hepatic Impairment Considerations

Mild to Moderate Hepatic Impairment (Child-Pugh Class A or B)

• No dose adjustment required—use standard dosing 2

Severe Hepatic Impairment (Child-Pugh Class C)

• Paxlovid is not recommended due to lack of safety and pharmacokinetic data 1, 2
• Trials excluded patients with severe liver impairment, so use with extreme caution only if benefits clearly outweigh risks 1, 4

Pregnancy and Breastfeeding

Pregnancy

• Paxlovid represents an option for pregnant individuals with COVID-19 to reduce risk of disease progression 1
• Despite uncertainty regarding potential serious adverse reactions, no reports of such reactions in parent or child have been documented in WHO Vigibase to date 1
• The benefit of reducing hospitalization and mortality should be weighed against theoretical risks 1

Breastfeeding

• Nirmatrelvir and ritonavir are present in breast milk in small amounts (less than 2% of maternal weight-adjusted dose) 2
• Estimated infant exposure is 0.16 mg/kg/day for nirmatrelvir (1.8% of maternal dose) and 0.006 mg/kg/day for ritonavir (0.2% of maternal dose) 2
• Breastfeeding individuals should follow clinical guidelines to avoid exposing the infant to COVID-19 while considering the benefits of breastfeeding 2

Contraception

• Ritonavir may reduce efficacy of combined hormonal contraceptives 2
• Advise patients to use an effective alternative contraceptive method or additional barrier method during treatment and for a period after completion 2

Critical Drug Interaction Management

Ritonavir is a potent CYP3A4 inhibitor causing drug-drug interactions during active treatment and possibly for several days after completion. 1, 4, 5

Before Prescribing

• Use the Liverpool COVID-19 Drug Interaction Tool to systematically check all concomitant medications 1, 6, 4
• Identify medications that are contraindicated, require dose adjustment, temporary discontinuation, or additional monitoring 2, 5

Contraindicated Medications

• Do not co-administer with drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions 2
• Do not co-administer with potent CYP3A inducers that may significantly reduce nirmatrelvir/ritonavir concentrations 2

Common Management Strategies

• Statins (particularly simvastatin and lovastatin) may require temporary discontinuation during the 5-day treatment course 4, 5
• CYP3A4 substrates with narrow therapeutic indices require temporary discontinuation or dose adjustment 6
• For immunosuppressants like JAK inhibitors, brief interruptions are generally well-tolerated without immediate disease flare 6

Monitoring Recommendations

• Monitor for common adverse effects: dysgeusia (altered taste) and diarrhea, which occur more frequently than placebo but rarely lead to discontinuation 1, 7
• Monitor for signs of hypersensitivity reactions including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome—discontinue immediately if these occur 2
• Monitor hepatic transaminases if clinically indicated, as hepatotoxicity has been reported with ritonavir 2
• In patients with renal impairment, reassess renal function during treatment if clinical deterioration occurs 4

Special Population Considerations

Pediatric Patients (12 to <18 years)

• For adolescents weighing ≥40 kg: use standard adult dosing of 300 mg/100 mg twice daily 8
• For adolescents weighing <40 kg: optimal dosing has not been established 2

Geriatric Patients

• No dose adjustment required based on age alone 2
• Clinical studies included patients ≥65 years with no overall safety differences compared to younger patients 2
• Pay particular attention to renal function assessment, as age-related decline may necessitate dose reduction 2

Common Pitfalls to Avoid

• Never prescribe nirmatrelvir without ritonavir—the combination is essential for adequate nirmatrelvir exposure 2
• Do not initiate treatment beyond 5 days of symptom onset—efficacy data only support early treatment 1, 2
• Do not overlook renal function assessment—failure to dose-adjust in moderate/severe renal impairment increases toxicity risk 2, 3
• Do not forget to counsel patients about drug interactions and the need to temporarily stop certain medications 4, 5
• Prescriptions should specify the numeric dose of each active ingredient to ensure proper renal dosing 2